Melatonin Supplementation in Iranian Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Exploring Oxidative Stress and Inflammation.

Abstract

<h4>Background</h4>Diabetes mellitus is a global health challenge characterized by oxidative stress (OS) and persistent inflammation, which contribute to the progression of complications. Melatonin, a multifaceted hormone known for its potent antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic intervention in diabetes. This systematic review and meta-analysis aimed to evaluate the effects of melatonin supplementation on crucial biomarkers of OS (malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH)) and inflammation (C-reactive protein (CRP)) in Iranian diabetic patients.<h4>Methods</h4>A thorough literature search was conducted until August 2023 in MEDLINE (PubMed), Embase, Web of Science, Cochrane Central, Magiran, and Scopus databases using keywords corresponding to MeSH, such as "diabetes," "melatonin," "oxidative stress," "randomized clinical trial," and "Iranians." The study focused on eight randomized controlled trials conducted on diabetic patients in Iran. The data were analyzed using the random-effects model, and the summary effect size was determined using the standardized mean difference (SMD).<h4>Results</h4>Our research indicates that melatonin supplementation led to significant reductions in CRP levels (SMD) = -1.74; 95% confidence interval (CI): -2.79, -0.69; <i>P</i> = 0.001) and MDA levels (SMD = -1.35; 95% CI: -2.17, -0.53; <i>P</i> = 0.001). Furthermore, the study found an increase in TAC levels (SMD = 2.79; 95% CI: 0.54, 5.04; <i>P</i> = 0.0006) and GSH levels (SMD = 1.86; 95% CI: 0.80, 2.93; <i>P</i> = 0.0006) following melatonin supplementation. In addition, subgroup analysis revealed that a lower dosage of 3-6 mg/day resulted in more pronounced effects, with a statistically significant difference observed in MDA reduction compared to higher doses.<h4>Conclusions</h4>Melatonin supplementation is a promising complementary strategy to attenuate OS and inflammation in diabetic patients.